Neurotensin (NT) is a vasoactive tridecapeptide which has been isolated from extracts of bovine hypothalami and small intestine. It is capable of a wide spectrum of biological effects which classify it as a "kinin". Administered intracisternally NT produces hypothermia in cold-exposed rats and mice. When injected intravenously NT induces hypotension, increased vascular permeability, hyperglycemia, hemoconcentration, and cyanosis in the anesthetized rat and also has been found to bring about increased secretion of ACTH, LH, FSH, and glucagon. NT has been shown to potently affect the intestinal vascular bed of the conscious dog and also to inhibit pentagastrin-induced gastric acid secretion in dogs with Pavlov pouches. Effects demonstrated in vitro include a chemotactic property toward human leukocytes and an ability to affect the contractility of the isolated rat duodenum, rat stomach strip, and guinea pig ileum. Structure-function studies indicate that the biological activity of NT resides primarily in its COOH-terminal region and that the COOH-terminal pentapeptide, H-Arg-Pro-Tyr-Ile-Leu-OH, has reduced potency but full intrinsic biological activity. Using radioimmunoassay and immunohistochemistry we have detected NT-related activity throughout the central nervous system (CNS) and digestive system of the rat, as well as in the chicken and rat thymus gland. NT-activity is located within neurons in the CNS and in endocrine-like cells of the gut and thymus. Recent chromatographic and immunochemical studies indicate that the NT-like peptide(s) present differ from NT, but appear to possess the COOH-terminal, biologically active portion of NT. Large forms of NT are also present in brain and intestinal extracts. We propose to isolate and identify the NT-like peptide(s) present in (a) bovine stomach (b) chicken or bovine thymus and to characterize the large forms in (c) bovine intestine. New structures will be prepared synthetically and characterized pharmacologically.